基于网络药理学探讨桑黄改善脂质代谢作用的机理
首发时间:2021-04-09
摘要:背景:桑黄具有极高的药用价值,现有研究表明其对改善脂质代谢具有积极作用,但作用机,理尚不明确。目的:基于网络药理学,探究桑黄改善脂质代谢机理研究。 方法:通过查阅文献和中药与化学成分数据库收集桑黄活性成分并利用Swiss ADME进行筛选。将筛选出的成分导入PharmMapper数据库中获得桑黄活性成分潜在靶点。在GeneCards、OMIM、Drugbank等数据库中以"Hyperlipidemia"(高脂血症),"Disturbed lipid metabolism"(脂质代谢)为关键词获取疾病潜在靶点。将活性成分潜在靶点与潜在靶点取交集获得药物与疾病的共有靶点,并以此为基础首先使用Cytoscape进行"桑黄-活性成分-共有靶点"网络的可视化构建,再通过STRING数据库生成蛋白质互作网络,最后Metascape数据库进行GO功能富集分析和KEGG通路富集分析,来探究桑黄改善脂质代谢机制。 结果:从桑黄中共筛选出19种有效活性成分,涉及143个靶点。从"Hyperlipidemia","Disturbed lipid metabolism"中查找出3212个靶点。其中药物与疾病相同的靶点共93个,分别为ANG、APCS、BCHE等。建立的"桑黄-活性成分-共有靶点"网络中包含桑黄的19种活性成分、93个靶点,并筛选出10种重要活性成分,包括m-hemipinic acid、asparagic acid、Sakuranetin等。通过网络拓扑和蛋白质互作网络分析筛选出30个核心靶点,包括REN、GSTP1、TPI1等。GO功能富集分析获得生物过程条目(BP)911个、细胞组成条目(CC)96个、分子功能条目(MF)35个。KEGG通路富集分析筛选出相关信号通路101条,包括PI3K-Akt信号通路、内分泌抵抗相关通路、胰岛素抵抗相关通路等。 结论:本项目得出桑黄中的活性成分可能通过作用于PPARG、RXRA等关键靶点影响PI3K-Akt signaling pathway、PPAR signaling pathway等15条通路对改善脂质代谢起调节作用。项目通过网络药理学的方法阐明其复杂的网络关系,其结果可与常规实验相结合更好地增加对改善脂质代谢机制分子层面的了解,为桑黄改善脂质代谢紊乱、治疗高脂血症等研究方向以及药物开发提供重要理论依据。?????
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Mechanism of Phellinus Igniarius Improving Iipid Metabolism Based on Network Pharmacology
Abstract:Background: Phellinus igniarius has very high medicinal value and existing studies have shown that it has a positive effect Study and Validation of Phellinus Igniarius to Improve Lipid Metabolism based on Network Pharmacologyon improving lipid metabolism, but the mechanism of action remains unclear. Objective: To explore the mechanism of Phellinus igniarius improving lipid metabolism based on network pharmacology. Methods: The active components of Phellinus igniarius were collected through literature review and database of traditional Chinese medicine and chemical constituents, and screened by SwissADME. The selected components were imported into pharmmapper database to obtain the potential targets of active componentsof Phellinus igniarius. In genecards, OMIM, drugbankand other databases, "hyperlipidemia" and "disturbed lipid metabolism" were used as keywords to obtain potential targets. Based on the intersection of potential targets of active ingredients and potential targets, the common targets of drugs and diseases were obtained. Based on that, the network of "Phellinus igniarius - active ingredients - common targets" was firstly visualized by using Cytoscape, and then the protein interaction network was generated by using STRING database. Finally, the GO function enrichment analysis and KEGG pathway enrichment analysis were carried out by using Metascape database to explore Phellinus igniarius improving the mechanism of lipid metabolism. Results: A total of 19 active components were screened from Phellinus igniarius, involving 143 targets. 3212 targets were found from "hyperlipidemia" and "distorted lipid metabolism". Among them, there are 93 targets with the same drug and disease, including ANG, APCs, BCHE, etc. The network of "Phellinus igniarius - active ingredients - common targets" includes one drug, 19 active ingredients, 93 targets, of which 10 important active ingredients were selected, including m-hemipinic acid, asparagic acid, sakuranetin, etc. Through network topology and protein interaction network analysis, 30 core targets were screened, including REN, GSTP1, TPI1, etc. By GO enrichment analysis, 911 biological process items (BP), 96 cell composition items (CC) and 35 molecular function items (MF) were obtained. KEGG pathway enrichment analysis screened 101 related signaling pathways, including PI3K Akt signaling pathway, endocrine resistance, insulin resistance and so on. Conclusion: The active components of Phellinus igniarius of this project may affect 15 pathways such as PI3K-Akt signaling pathway and PPAR signaling pathway by acting on PPARG, SOD2, RXRA, ALB, MAPK8 and so on, and play a regulatory role in improving lipid metabolism. This project may explain complex network relations by the method of network pharmacology. The network pharmacology research results can be combined with conventional experiments to better help improve the understanding of improving lipid metabolism mechanism, from the molecular level and provide significant theoretical basis on research directions such as improving lipid metabolism disorder and treating hyperlipidemia as well as drug development.
Keywords: Pharmacology;Network pharmacology;Phellinus igniarius;Lipid metabolism;Signaling pathways
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